formation of vitamin D3 itself. Vitamin D3 can also be converted to nonactive forms.

The absolute percentage of circulating 25OHD that arises from cutaneous synthesis versus oral intake of vitamin D in the free-living North American population cannot be clearly specified. Individuals living at Earth’s poles during winter months and submariner crew members with very limited or no measurable UVB exposure have detectable levels of 25OHD in blood, arising from dietary sources and likely from previously synthesized and stored vitamin D. This topic is further explored in the section below that focuses on serum 25OHD.

METABOLISM OF VITAMIN D

Absorption

Owing to its fat-soluble nature, dietary vitamin D (either D2 or D3) is absorbed with other dietary fats in the small intestine (Haddad et al., 1993; Holick, 1995). The efficient absorption of vitamin D is dependent upon the presence of fat in the lumen, which triggers the release of bile acids and pancreatic lipase (Weber, 1981, 1983). In turn, bile acids initiate the emulsification of lipids, pancreatic lipase hydrolyzes the triglycerides into monoglycerides and free fatty acids, and bile acids support the formation of lipid-containing micelles, which diffuse into enterocytes. Early studies demonstrated that radiolabeled vitamin D3 appeared almost exclusively in the lymphatics and in the chylomicron fraction of plasma; as well, subjects with impaired bile acid release or pancreatic insufficiency both demonstrated significantly reduced absorption of vitamin D (Thompson et al., 1966; Blomstrand and Forsgren, 1967; Compston et al., 1981). Subsequently, other clinical and experimental animal studies confirmed that vitamin D is most efficiently absorbed when consumed with foods containing fat (Weber, 1981; Johnson et al., 2005; Mulligan and Licata, 2010) and, conversely, that a weight-loss agent that blocks fat absorption also impairs the absorption of vitamin D (James et al., 1997; McDuffie et al., 2002). The optimal amount of fat required for maximal absorption of vitamin D has not been determined.

Within the intestinal wall, vitamin D, cholesterol, triglycerides, lipoproteins, and other lipids are packaged together into chylomicrons. Importantly, while a fraction of newly absorbed intestinal vitamin D is also transported along with amino acids and carbohydrates into the portal system to reach the liver directly, the main pathway of vitamin D uptake is incorporation into chylomicrons that reach the systemic circulation via the lymphatics. Chylomicron lipids are metabolized in peripheral tissues that express lipoprotein lipase, but particularly in adipose tissue and